Phenomena which allow the malignant clone in acute myelogenous leukemia (AML) to prosper are undoubtedly diverse. I postulate that factors in AML sera may play a role in promoting the malignancy. In preliminary studies I have reported that sera from AML patients, but not controls, support viability of AML cells in liquid culture. After exposure to immunoglobulin-binding strains of killed Staphylococcus aureus (S. aureus), the same sera no longer support viability of either autologous or allogeneic AML blasts. In contrast, the growth of lymphoblasts from acute lymphoblastic leukemia (ALL) patients is not affected by such plasma perturbation. Moreover, neither normal sera nor ALL sera alter AML blast viability either before, or after, exposure to S. aureus. Since readdition of untreated AML plasma to S. aureus-adsorbed plasma rejuvenates AML blast viability, either a substance is present in untreated AML sera which is necessary for cell viability or cytotoxicity "blocking factors' are removed by S. aureus. Recently I have found tumor regression in three animals with lymphoma ot leukemia in which 10 to 20% of plasma volume was reinfused after ex vivo exposure to killed S. aureus suggesting again that removal of cytotoxicity "blocking factors" or of growth factors modulates in vivo tumor viability as well. The objectives of my proposed research are to study the mechanism by which AML sera support blast viability and growth before, but not after, exposure to S. aureus by further investigating the respective roles of growth factors, or, conversely, of unmasked complement, antibody, or cell-mediated cytotoxicity. Both liquid and soft agar cell culture techniques will be utilized. Growth promoting and cytotoxic activities will be sought in various fractions of treated and untreated AML sera prepared both by means of size exclusion filtration and column chromatography. Furthermore, AML patients will be followed with serial cultures in an attempt to correlate clinical course with changing plasma characteristics; these studies will also assay changes in cell susceptibility to plasma manipulation as the disease progresses. Finally, the efficacy and safety of ex vivo perfusion of plasma with killed S. aureus will be studied in reinfusted animals bearing malignancies.